RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Development and Validation of a Toxoplasma Infection-Associated Risk Model for Prognostic Stratification and Treatment Guidance in Glioma.
Development and Validation of a Toxoplasma Infection-Associated Risk Model for Prognostic Stratification and Treatment Guidance in Glioma.
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胶质瘤是预后不良的侵袭性脑肿瘤。刚地弓形虫(T. gondii)相关转录程序对胶质瘤的贡献尚不清楚。我们从神经上皮细胞转录组中鉴定了T. gondii感染相关基因,将其映射到TCGA和CGGA胶质瘤数据集中,并通过RT-qPCR验证了其表达。通过Cox和LASSO回归构建了预后特征(TGRisk),并在独立队列中进行了验证。进行了功能、免疫和药物敏感性分析。共鉴定出40个感染相关基因,富集于应激反应、microRNA调控、核糖体生物合成和代谢。13基因TGRisk模型显著区分了高风险组和低风险组之间的生存。结合TGRisk与临床特征的列线图提高了预测准确性。高风险肿瘤显示免疫激活以及CD8 + T细胞、Tregs、巨噬细胞和中性粒细胞的更高浸润,而低风险肿瘤显示神经信号传导和NK细胞活性增强。药物敏感性预测提示低风险患者对temozolomide和bortezomib的反应更好,而高风险患者对dasatinib和ruxolitinib更敏感。
我们开发了一种新的T. gondii感染相关基因特征,可按预后、免疫特征和治疗脆弱性对胶质瘤患者进行分层。这些发现提示了宿主与T. gondii之间的相互作用,并为患者分层和个体化治疗提供了潜在生物标志物。
Gliomas are aggressive brain tumors with poor prognosis. The contribution of Toxoplasma gondii (T. gondii) -related transcriptional programs to glioma remains unclear.
We identified T. gondii infection-related genes from neuroepithelial cell transcriptomes, mapped them to TCGA and CGGA glioma datasets, and validated their expression via RT-qPCR. A prognostic signature (TGRisk) was constructed via Cox and LASSO regression and validated across independent cohorts. Functional, immune, and drug sensitivity analyses were conducted. Forty infection-related genes were identified, enriched in stress responses, microRNA regulation, ribosome biogenesis, and metabolism.
The 13-gene TGRisk model significantly separated survival between high- and low-risk groups. A nomogram combining TGRisk with clinical features improved prediction accuracy. High-risk tumors showed immune activation and higher infiltration of CD8 + T cells, Tregs, macrophages, and neutrophils, while low-risk tumors showed enhanced neuronal signaling and NK cell activity. Drug sensitivity prediction suggested low-risk patients were more responsive to temozolomide and bortezomib, whereas high-risk patients were more sensitive to dasatinib and ruxolitinib.
We developed a novel T. gongdii infection-related gene signature that stratifies glioma patients by prognosis, immune features, and therapeutic vulnerabilities.
These findings suggest host- T. gondii interactions and a potential biomarker for patient stratification and personalized therapy.
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